Down syndrome is the most common genetic syndrome resulting in intellectual disability. Recent evidence from studies of brain structure and function in humans with Down syndrome and animal models of Down syndrome identifies the hippocampus as a brain region that is particularly impacted by Down syndrome. One important function of the hippocampus and surrounding regions is to assist in learning spatial layouts and navigating the environment, including explicit and implicit learning of spatial/contextual information. This is the first research specifically designed to evaluate the performance of persons with Down syndrome on wayfinding, and represents an extremely important area of investigation given the significance of wayfinding to independent functioning. The long-term objectives of our research are to identify specific areas of difficulty in wayfinding abilities of persons with Down syndrome and identify pathways to remediation of identified problems. We expect to find that persons with Down syndrome will exhibit severe deficiencies in wayfinding performance. In the proposed research we compare the performance of two groups of 12 - 21 year old youths: one group with Down syndrome and one group of mixed-etiology. These groups are also compared to typically developing children matched on nonverbal ability. These comparisons will allow us to determine whether observed deficiencies in wayfinding are syndrome specific with respect to Down syndrome. Specific Aim 1 is to demonstrate a deficiency in wayfinding performance of persons with Down syndrome relative to IQ and TD controls. Specific Aim 2 is to evaluate the relationships between wayfinding performance and two hippocampal system functions (episodic learning and implicit contextual learning) for persons with Down syndrome relative to IQ and TD controls. Specific Aim 3 is to evaluate the relationships between wayfinding performance and three prefrontal functions (executive function, planning and inhibition) for persons with Down syndrome relative to IQ and TD controls. If we find that prefrontal functions play a larger role in wayfinding for persons with Down syndrome relative to IQ and TD controls and we can use that information as a basis for future interventions. PUBLIC HEALTH RELEVANCE: Down syndrome is the most common genetic syndrome of intellectual ability. We have identified wayfinding as an important skill of independent living that is likely to be deficient in Down syndrome. The research of the proposed application is designed to identify specific areas of difficulty in wayfinding abilities of persons with Down syndrome and identify pathways to remediation of identified problems.